Expression and sub-cellular localization of the CCAAT/enhancer binding protein alpha in relation to postnatal development and malignancy of the prostate.
Expression and sub-cellular localization of the CCAAT/enhancer binding protein alpha in relation to postnatal development and malignancy of the prostate.
复制标题
CCAAT/增强子结合蛋白α的表达和亚细胞定位与产后发育和前列腺恶性肿瘤的关系。
DOI:
10.1002/pros.20779
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发表时间:
2008
期刊:
影响因子:
--
通讯作者:
Ratnam,Manohar
中科院分区:
文献类型:
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作者:
Zhang,Juan;Wilkinson,JohnErby;Gonit,Mesfin;Keck,Rick;Selman,Steven;Ratnam,Manohar
BackgroundC/EBPα is a critical mediator of terminal differentiation and a tumor suppressor through its strong antiproliferative actions on cell cycle regulatory proteins. C/EBPα also appears to regulate androgen receptor (AR) AR signaling. There, is a paucity of information on the expression and sub‐cellular localization of C/EBPα in normal mouse and human prostate and in prostate cancer.MethodsImmunohistochemistry of tissues including tissue arrays, quantitative polymerase chain reaction and mRNA expression database mining.ResultsIn the mouse prostate epithelium, C/EBPα was present at 1 week postnatal localized in the cytosol, began to show nuclear localization at 8 weeks and continued to show prominent nuclear expression at 10 weeks and beyond; C/EBPα mRNA was expressed at all ages. In humans, C/EBPα showed prominent nuclear localization from peripubescence up to middle age but was sequestered in the cytosol in older individuals; the mRNA level for C/EBPα remained essentially unchanged. Most prostate adenocarcinomas expressed a range of levels of C/EBPα mRNA and protein that were relatively high in metastatic tumors in a manner that correlated with AR expression; however, most cells showed C/EBPα sequestered in the cytosol.ConclusionsTemporal changes in sub‐cellular localization of C/EBPα are consistent with a role in prostate differentiation and as a prostate tumor suppressor; the cytoplasmic sequestration of C/EBPα, unique to older human prostates, is arguably a permissive condition for the greater frequency of proliferative disorders of the prostate. In malignant prostate C/EBPα may be available to regulate AR signaling through transient changes in its sub‐cellular localization. Prostate 68: 1206–1214, 2008. © 2008 Wiley‐Liss, Inc.